Microbial modifications with Lycium barbarum L. oligosaccharides decrease hepatic fibrosis and mitochondrial abnormalities in mice.

BACKGROUND: Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied. PURPOSE: Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis. STUDY DESIGN AND METHODS: Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices). RESULTS: The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and ß-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis. CONCLUSION: These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.

Preparation and application of an imidazolium-based poly (ionic liquid) functionalized silica sorbent for solid-phase extraction of parabens from food samples.

In this work, an imidazolium-based poly (ionic liquid) (poly(1-octyl-3-vinyl- imidazolium naphthalene sulfonate)) functionalized silica (poly(C8VIm+NapSO3-) @SiO2) was successfully prepared for the determination of parabens in food samples. The prepared poly(C8VIm+NapSO3-)@SiO2 was characterized by Fourier transform infrared spectrometry (FT-IR), X-ray photoelectron spectrogram (XPS) and Scanning electron microscopy (SEM). The simulation calculation results indicated that the suitable binding energies were between the polymeric ionic liquids and parabens, and the main interactions for extraction were hydrogen bonding, electrostatic and π-π stacking interactions. In addition, compared with commercial extraction materials, the prepared poly(C8VIm+NapSO3-)@SiO2 sorbent showed comparable or even better extraction performance towards parabens. The effective parameters were optimized by a combination of the univariate method and Box-Behnken design (BBD). Under the optimum conditions, coupled with high performance liquid chromatography (HPLC), wide linear ranges (1.0-800 µg L-1), good linearity (R2 ≥ 0.9997) and low limits of detection (0.1 µg L-1) were obtained. In addition, the intra-day and inter-day relative standard deviations (RSDs) were all lower than 6.3%. Moreover, the proposed method was successfully used for the determination of parabens in food samples and satisfactory recoveries in the range of 76.9-97.4% were obtained. The results indicated that the proposed method had good sensitivity, accuracy and precision for the detection of parabens in food samples.

Effects of polyols with different hydroxyl numbers on the structure and properties of starch straws.

To study the relationship between the number of hydroxyl groups of polyols and the plasticizing effect, the effects of different polyols including ethylene glycol, glycerol, erythritol, xylitol and sorbitol on the structure and properties of corn starch straws were analyzed and compared. The results showed that the addition of plasticizer significantly improved the performance of starch straws, which greatly improved the mechanical properties, water absorption rate (WAR) and thermal stability. However, there was no linear relationship between the plasticizing effect on starch straws and the number of hydroxyl groups in plasticizers. Fourier transform infrared (FTIR) results showed that erythritol formed the strongest intermolecular interaction with starch. Starch straws with erythritol (S-ERY) had the highest bending force (Fb = 25.78 N) and the lowest WAR. Starch straws with glycerol (S-GLY) showed the lowest relative crystallinity (RC = 12.87 %) and the highest temperature of the maximum degradation (Tdmax = 302.1 °C). In addition, after storing for 180 days, S-GLY showed higher modulus of elasticity in bending (Eb = 4.26 N/cm) and a uniform surface.

Synergistic effect of enzymatic pre-treatment and amylose-lipid complex construction on the physicochemical properties of maize starch.

In this study, the effects of maltogenic amylase (MAA) pre-treatment and starch-fatty acid complex construction on the physicochemical properties of maize starch (MAS) were investigated. The average chain length of MAA-modified MAS was found to decrease from 18.15 to 14.92. Moreover, MAA pre-treatment of starch induced the formation of a V-type complex. This behaviour was demonstrated by the higher diffraction intensity, enzymatic resistance and short-range ordering of the samples pre-treated with MAA compared with unmodified samples. X-ray diffraction and rheological analysis revealed that the re-crystallisation peak intensities and storage modulus of MAA-MAS-lauric acid (LA)/stearic acid (SA) complexes were lower than those of MAA-starches, MAS-LA/SA complexes and control. The rate of starch re-crystallisation was effectively decreased by the combination of MAA pre-treatment and V-type complex construction. The anti-retrogradation (long-term) characteristics of the tested samples were in the following order: MAA-MAS-LA/SA complexes > MAA-starches > MAS-LA/SA complexes > control.

Starch/polyvinyl alcohol with ionic liquid/graphene oxide enabled highly tough, conductive and freezing-resistance hydrogels for multimodal wearable sensors.

With ever-growing demand for eco-friendly materials for wearable electronics, biopolymer-based hydrogels have drawn significant attention. As one of the most abundant and biodegradable biopolymers, starch-based hydrogels have a great potential for wearable electronics. However, mechanical fragility, low conductivity and subzero freeze restrict their applications. Here, a multifunctional hydrogel was facilely fabricated by integrating ionic liquid and graphene oxide into potato starch/polyvinyl alcohol skeleton via a green physical-crosslinking method. The abundant hydrogen-bond and electrostatic interactions endowed the hydrogel with excellent stretchability (657.5 %), strength (0.64 MPa), high conductivity (1.98 S·m-1) and good anti-freezing property (< -20 °C). Multiple characterizations and theoretical simulation (DFT) were combined to understand and confirm the interactions among different components. Taking advantage of these properties, multimodal wearable sensors were constructed for sensing tension (gauge factor: 6.04), compression (gauge factor: 3.27) and temperature (sensitivity: 0.71 %/°C), which are applied for monitoring human motion, daily-life pressure and body temperature. The sensor had a good anti-fatigue property with stable signals during 2000 cycles. Moreover, the sensor can effectively recognize handwriting and perform human-computer interaction. This work provides a promising route to develop sustainable and multifunctional biopolymer hydrogels for wearable sensors with versatile applications in human health, exercise monitors and soft robots.

Early-life noise exposure causes cognitive impairment in a sex-dependent manner by disrupting homeostasis of the microbiota-gut-brain axis.

Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.

Maltogenic amylase: Its structure, molecular modification, and effects on starch and starch-based products.

Maltogenic amylase (MAA) (EC3.2.1.133), a member of the glycoside hydrolase family 13 that mainly produces α-maltose, is widely used to extend the shelf life of bread as it softens bread, improves its elasticity, and preserves its flavor without affecting dough processing. Moreover, MAA is used as an improver in flour products. Despite its antiaging properties, the hydrolytic capacity and thermal stability of MAA can't meet the requirements of industrial application. However, genetic engineering techniques used for the molecular modification of MAA can alter its functional properties to meet application-specific requirements. This review briefly introduces the structure and functions of MAA, its application in starch modification, its effects on starch-based products, and its molecular modification to provide better insights for the application of genetically modified MAA in starch modification.

Dapagliflozin attenuates cardiac remodeling and dysfunction in rats with ß-adrenergic receptor overactivation through restoring calcium handling and suppressing cardiomyocyte apoptosis.

Background: Long-term ß-adrenergic receptor (ß-AR) activation can impair myocardial structure and function. Dapagliflozin (DAPA) has been reported to improve clinical prognosis in heart failure patients, whereas the exact mechanism remains unclear. Here, we investigated the effects of DAPA against ß-AR overactivation toxicity and explored the underlying mechanism.Methods and Results: Rats were randomized to receive saline + placebo, isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) + placebo, or ISO + DAPA (1 mg/kg/day, intragastrically) for 2-week. DAPA treatment improved cardiac function, alleviated myocardial fibrosis, prevented cardiomyocytes (CMs) apoptosis, and decreased the expression of ER stress-mediated apoptosis markers in ISO-treated hearts. In isolated CMs, 2-week ISO stimulation resulted in deteriorated kinetics of cellular contraction and relaxation, increased diastolic intracellular Ca2+ level and decay time constant of Ca2+ transient (CaT) but decreased CaT amplitude and sarcoplasmic reticulum (SR) Ca2+ level. However, DAPA treatment prevented abnormal Ca2+ handling and contractile dysfunction in CMs from ISO-treated hearts. Consistently, DAPA treatment upregulated the expression of SR Ca2+-ATPase protein and ryanodine receptor 2 (RyR2) but reduced the expression of phosphorylated-RyR2, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and phosphorylated-CaMKII in ventricles from ISO-treated rats.Conclusion: DAPA prevented myocardial remodeling and cardiac dysfunction in rats with ß-AR overactivation via restoring calcium handling and suppressing ER stress-related CMs apoptosis.

Research on microstructural-mechanical and shearing properties of castor seed during mechanical extraction.

Castor seed oil, as an important biomass fuel, has attracted extensive attention worldwide due to inclusive applications. Castor seed screw mechanical extraction is in fact seed shear damage and oil output. Seed shearing mechanism has been investigated with a developed tribometer. Influences of pressing load, shearing speed, roller roughness were analyzed. Castor seed structural damage was in-situ observed with optical microscope, and in-depth analyzed with Scanning Electron Microscopy and Energy Dispersive Spectroscopy. The results reveal that shear interaction can be divided into three stages: coat damage, transition shearing and endosperm oil output. Seed shear mechanism includes coat peeling, endosperm plowing, tissue transferring and oil lubrication. High pressing load leads to more damage of coat and endosperm, causing more oil to flow out. With shearing speed increasing, coat is easily peeled, obvious endosperm shear plowing and oil lubrication happened in contact area. Coat damage by high roughness leads more oil output. Castor oil enters the contact area and work as lubricant, leading to the decrease of friction resistance.

Transcriptome Analysis Reveals the Immunoregulatory Activity of Rice Seed-Derived Peptide PEP1 on Dendritic Cells.

Some food-derived bioactive peptides exhibit prominent immunoregulatory activity. We previously demonstrated that the rice-derived PEP1 peptide, GIAASPFLQSAAFQLR, has strong immunological activity. However, the mechanism of this action is still unclear. In the present study, full-length transcripts of mouse dendritic cells (DC2.4) treated with PEP1 were sequenced using the PacBio sequencing platform, and the transcriptomes were compared via RNA sequencing (RNA-Seq). The characteristic markers of mature DCs, the cluster of differentiation CD86, and the major histocompatibility complex (MHC-II), were significantly upregulated after the PEP1 treatment. The molecular docking suggested that hydrogen bonding and electrostatic interactions played important roles in the binding between PEP1, MHC-II, and the T-cell receptor (TCR). In addition, the PEP1 peptide increased the release of anti-inflammatory factors (interleukin-4 and interleukin-10) and decreased the release of pro-inflammatory factors (interleukin-6 and tumor necrosis factor-α). Furthermore, the RNA-seq results showed the expression of genes involved in several signaling pathways, such as the NF-κB, MAPK, JAK-STAT, and TGF-ß pathways, were regulated by the PEP1 treatment, and the changes confirmed the immunomodulatory effect of PEP1 on DC2.4 cells. This findings revealed that the PEP1 peptide, derived from the byproduct of rice processing, is a potential natural immunoregulatory alternative for the treatment of inflammation.

Advanced Glycation End Products: A Comprehensive Review of Their Detection and Occurrence in Food.

The Maillard reaction (MR) is a complicated chemical process that has been extensively studied. Harmful chemicals known as advanced glycation end products (AGEs), with complex structures and stable chemical characteristics, are created during the final stage of the MR. AGEs can be formed both during the thermal processing of food and in the human body. The number of AGEs formed in food is much higher compared to endogenous AGEs. A direct connection exists between human health and the build-up of AGEs in the body, which can result in diseases. Therefore, it is essential to understand the content of AGEs in the food we consume. The detection methods of AGEs in food are expounded upon in this review, and the advantages, disadvantages, and application fields of these detection methods are discussed in depth. Additionally, the production of AGEs in food, their content in typical foods, and the mechanisms influencing their formation are summarized. Since AGEs are closely related to the food industry and human health, it is hoped that this review will further the detection of AGEs in food so that their content can be evaluated more conveniently and accurately.

Dual cross-linked starch hydrogel for eugenol encapsulation and the formation of hydrogen bonds on textural hydrogel.

Physical and chemical cross-linked hydrogels combining N, N'-Methylenebisacrylamide (MBA)-grafted starch (MBAS) and sorbitol were successfully prepared and encapsulated with eugenol in this work. The dense porous structure with diameter of 10-15 µm and strong skeleton after restructuring inside the hydrogel was confirmed by SEM. The band shifts between 3258 cm-1 and 3264 cm-1 clarified the presence of a large number of hydrogen bonds in physical and chemical cross-linked hydrogels. The robust structure of the hydrogel was confirmed by mechanical and thermal property measurements. Molecular docking techniques were used to help understand the bridging pattern between three raw materials and to assess the advantageous conformation, which demonstrate sorbitol is beneficial to improve the characteristics of textural hydrogel by the formation of hydrogen bonds, creating a denser network, structural recombination and new intermolecular hydrogen bonds between starch and sorbitol afforded considerably junction zones. Compared to ordinary starch-based hydrogels, eugenol-loaded starch-sorbitol hydrogels (ESSG) exhibited a more attractive internal structure, swelling properties, viscoelasticity. Moreover, the ESSG showed excellent antimicrobial activity for typical undesired microorganisms in foods.

T4PPVB-COP composite-driven innovative electrochemiluminescence aptasensor for ultra-sensitive detection of chlorpyrifos.

Herein, an enhanced electrochemiluminescence (ECL) aptasensor driven by a complex (T4PPVB-COP@CdS QDs) with large specific surface area and high stability was constructed for highly sensitive detection of chlorpyrifos (CPF), using electrostatic interactions and signal amplification techniques. In the presence of CPF, the specific binding between the aptamer and CPF caused partial detachment of the aptamer from the sensor, thus restoring the ECL signal. Notably, gold nanoparticles functionalized with streptavidin (SA) as signal enhancers further amplified the ECL signal in specific interactions with aptamers, thereby improving the sensitivity of the assay. Based on this, the proposed ECL aptasensor demonstrated significant detection performance for CPF with a linear range of 1-107 pg/mL and a LOD of 0.34 pg/mL. Furthermore, the feasibility of the ECL aptasensor was validated by the detection and analysis of CPF in real samples, which also provided a broad reference value for bioanalysis.

Dual-Ion Co-Regulation System Enabling High-Performance Electrochemical Artificial Yarn Muscles with Energy-Free Catch States.

Artificial yarn muscles show great potential in applications requiring low-energy consumption while maintaining high performance. However, conventional designs have been limited by weak ion-yarn muscle interactions and inefficient "rocking-chair" ion migration. To address these limitations, we present an electrochemical artificial yarn muscle design driven by a dual-ion co-regulation system. By utilizing two reaction channels, this system shortens ion migration pathways, leading to faster and more efficient actuation. During the charging/discharging process, [Formula: see text] ions react with carbon nanotube yarn, while Li+ ions react with an Al foil. The intercalation reaction between [Formula: see text] and collapsed carbon nanotubes allows the yarn muscle to achieve an energy-free high-tension catch state. The dual-ion coordinated yarn muscles exhibit superior contractile stroke, maximum contractile rate, and maximum power densities, exceeding those of "rocking-chair" type ion migration yarn muscles. The dual-ion co-regulation system enhances the ion migration rate during actuation, resulting in improved performance. Moreover, the yarn muscles can withstand high levels of isometric stress, displaying a stress of 61 times that of skeletal muscles and 8 times that of "rocking-chair" type yarn muscles at higher frequencies. This technology holds significant potential for various applications, including prosthetics and robotics.

Pretension-Free and Self-Recoverable Coiled Artificial Muscle Fibers with Powerful Cyclic Work Capability.

Similar to natural muscle fibers, coiled artificial muscle fibers provide a straightforward contraction. However, unlike natural muscle fibers, their recovery from the contracted state to the initial state requires high stress, resulting in almost zero work during a full actuation cycle. Herein, a self-recoverable coiled artificial muscle fiber was prepared by conformally coating an elastic carbon nanotube (CNT) fiber with a very thin liquid crystal elastomer (LCE) sheath. The as-obtained muscle fiber demonstrated excellent actuation properties comprising 56.9% contractile stroke, 1522%/s contraction rate, 7.03 kW kg-1 power density, and 32,000 stable cycles. The LCE chains were helically aligned in a nematic phase, and the phase change of the LCE caused by Joule heating drove the actuation process. Moreover, the LCE/CNT fiber had a well-separated, torsionally stable, and elastic coiled structure, which permitted large contractile strokes and acted as an elastic template for external-stress-free recovery. Thus, the use of self-recoverable muscle fibers to mimic the natural muscles for object dragging, multidirectional bending, and quick striking was demonstrated.

Alanine Substitution to Determine the Effect of LR5 and YR6 Rice Peptide Structure on Antioxidant and Anti-Inflammatory Activity.

The relationship between the structure of peptides LR5 (LHKFR) and YR6 (YGLYPR) and their antioxidant and anti-inflammatory activity remains unclear. Herein, leucine, tyrosine, proline, and phenylalanine at different positions in the peptides were replaced by Alanine (Ala), and two new pentapeptides (AR5 and LAR5) and four hexapeptides (AGR6, YAR6, YLR6, and YGR6) were obtained. The effect of Ala replacement on the hydrophobicity, cytotoxicity, NO inhibition rate, and active oxygen radical scavenging ability of these peptides and their antioxidant and anti-inflammatory abilities were investigated. The results indicated that the hydrophobicity of the peptides was associated with their amino acid composition and their specific sequence. However, hydrophobicity had no significant effect on cytotoxicity. Ala replacement was shown to enhance hydrophobicity and consequently increased the antioxidant and anti-inflammatory activity of the peptides. The molecular docking studies indicated that the amino acid interactions of the peptide with the Keap1 protein influenced the hydrophobicity and thus affected the antioxidant activity of the peptide.

d-Glucosamine induces circadian phase delay by promoting BMAL1 degradation through AMPK/mTOR pathway.

Circadian rhythms are closely linked to the metabolic network through circadian feedback regulation. The hexosamine biosynthetic pathway (HBP) is a branch of glucose metabolism that affects circadian rhythms through the O-linked N-acetylglucosamine modification (O-GlcNAcylation) of clock proteins. Here, we found out that, among the downstream metabolites regulated by d-glucosamine (GlcN) in HBP salvage pathway, only GlcN is able to induce circadian phase delay both in vitro and in vivo. Mechanistic studies indicated that the phase-shift induced by GlcN is independent of O-GlcNAcylation. Instead, GlcN selectively up-regulates p-AMPK activity, leading to the inhibition of mTOR signaling pathway, and thus down-regulation of p-BMAL1 both in human cell line and mouse tissues. Moreover, GlcN promoted BMAL1 degradation via proteasome pathway. These findings reveal a novel molecular mechanism of GlcN in regulating clock phase and suggest the therapeutic potential of GlcN as new use for an old drug in the future treatment of shift work and circadian misalignment.

Digestibility, structural and physicochemical properties of microcrystalline butyrylated pea starch with different degree of substitution.

In this study, microcrystalline butyrylated pea starch (MBPS) with higher contents of resistant starch (RS) was synthesized via esterification with butyric anhydride (BA) using microcrystalline pea starch (MPS) as the raw material. With the addition of BA, the new characteristic peaks appeared at 1739 cm-1 and 0.85 ppm obtained from FTIR and 1H NMR, respectively, and increased with the higher degree of BA substitution. Moreover, an irregular shape of MBPS, such as condensed particles and more cracks or fragments, had been observed by SEM. Further, the relative crystallinity of MPS increased then native pea starch and decreased with the reaction of esterification. MBPS had higher decomposition onset temperature (To) and temperature of maximum decomposition (Tmax) with increasing DS values. Simultaneously, an increasing trend RS content from 63.04 % to 94.11 % and a decreasing trends in rapidly digestible starch (RDS) and slowly digestible starch (SDS) contents of MBPS were recorded with increasing DS values. MBPS samples showed higher production capacity of butyric acid ranging from 553.82 µmol/L to 892.64 µmol/L during the fermentation process. Compared with MPS, the functional properties of MBPS were significantly improved.

Effects of different ratios of mannitol to sorbitol on the functional properties of sweet potato starch films.

Sorbitol as a plasticizer is easily crystallized from starch film, resulting in the reduction in plasticizing effect. To improve the plasticizing performance of sorbitol in starch films, mannitol, an acyclic hexahydroxy sugar alcohol, was used to cooperate with sorbitol. The effects of different ratios of mannitol (M) to sorbitol (S) as a plasticizer on mechanical properties, thermal properties, water resistance and surface roughness of sweet potato starch films were investigated. The results showed that the surface roughness of starch film with M:S (60:40) was the smallest. The number of hydrogen bonds between plasticizer and starch molecule was proportional to the mannitol content starch film. With the decrease of mannitol contents, the tensile strength of starch films gradually decreased except for M:S (60:40). Moreover, the transverse relaxation time value of starch film with M:S (100:0) was the lowest, indicating that it had the lowest degree of freedom of water molecules. Starch film with M:S (60:40) is the most effective in delaying the retrogradation of starch film. This study offered a new theoretical basis that different ratios of mannitol to sorbitol improve different performances of starch films.

Altered Anterior Insular Metabolic Connectivity in Asymptomatic MAPT P301L Carriers.

BACKGROUND: The insula is the predominant brain region impaired in behavioral variant frontotemporal dementia (bvFTD). However, structural and functional changes in the sub-insula in the asymptomatic stage of bvFTD are unknown. OBJECTIVE: To describe structural and functional changes in insula subregions in asymptomatic carriers of the P301L mutation of the microtubule-associated protein tau (MAPT) gene and patients with bvFTD. METHODS: Six asymptomatic MAPT P301L mutation carriers and 12 MAPT negative control subjects of the same pedigree were enrolled, along with 30 patients with a clinical diagnosis of bvFTD and 30 matched controls. All subjects underwent hybrid positron emission tomography/magnetic resonance imaging. Atlas-based parcellation using a fine-grained Brainnetome Atlas was conducted to assess gray matter (GM) volume, metabolism, and metabolic connectivity in the sub-insula (region of interest). RESULTS: There was no significant GM atrophy or hypometabolism in insula subregions in asymptomatic MAPT P301L carriers, although decreased metabolic connectivity between vIa-middle temporal gyrus, vIa-temporal poles, dIa-middle temporal gyrus and dIa-temporal poles; and increased connectivity between vIa-orbitofrontal, vIa-dorsal lateral superior frontal gyrus, and dIa-orbitofrontal and dIa-dorsal lateral superior frontal gyrus were observed. Patients with bvFTD had significant atrophy and hypometabolism in all insula subregions and decreased metabolic connectivity in the whole brain, including vIa/dIa-middle temporal and vIa/dIa-temporal poles. The standardized uptake value ratios of vIa and dIa were negatively associated with Frontal behavior inventory disinhibition scale scores. CONCLUSION: Metabolic connectivity is altered in vIa and dIa subregions of the sub-insula in MAPT P301L mutation carriers before the occurrence of atrophy, hypometabolism, and clinical symptoms.